Staging and therapy of cutaneous melanoma patients with sentinel lymph node (SLN) biopsies and the use of systemic adjuvant therapy in those with high risk primaries and/or regional lymph node metastases lately have become commonplace, although neither has been shown unequivocally to improve survival. It is both timely and important to develop prognostic models that have potential utility for the design of efficient clinical trials and for clinical management of patients with melanoma. The objective of this project is to develop prognostic models using a rigorously documented and carefully followed cohort of over 5,500 melanoma patients assembled since 1972 and an archive of tissue blocks containing a representative sample of their primary lesions. The application of novel biostatistical methods using clinical and new immunohistologic data will allow us to achieve our explicit goals. To protect patients with "minimal risk" melanomas from the morbidity and cost of excessive investigation and therapy, in the first specific aim we will test the hypothesis that invasive melanoma without metastatic capacity can be identified using currently available, easily employed, and readily interpreted clinical, histologic and immunohistologic prognostic variables. To better calibrate investigation and management of patients with metastatic capacity by clinical trialists and clinicians, in the second specific aim we will develop multivariable prognostic models for predicting the likelihood of a SLN biopsy revealing melanoma and of metastasis-free survival after regional surgical staging and therapy. To optimize surveillance for additional primary melanomas in follow-up, in the third specific aim we will develop multivariable prognostic models for predicting the occurrence or a second primary. To promote the use of these models by clinical trialists and clinicians, we will develop individualized patient probabilities of the occurrence of clinically relevant events that can be used in trial design and clinical decision making.